text: In 2014 dabigatran remains the only approved oral DTI and is therefore the only DTI alternative to the vitamin K antagonists. There are, however, some novel oral anticoagulant drugs that are currently in early and advanced stages of clinical development. Most of those drugs are in the class of direct factor Xa inhibitors, but there is one DTI called AZD0837, which is a follow-up compound of ximelgatran that is being developed by AstraZeneca. It is the prodrug of a potent, competitive, reversible inhibitor of free and fibrin-bound thrombin called ARH0637.  The development of AZD 0837 is discontinued. Due to a limitation identified in long-term stability of the extended-release AZD0837 drug product, a follow-up study from ASSURE on stroke prevention in patients with non-valvular atrial fibrillation, was prematurely closed in 2010 after 2 years. There was also a numerically higher mortality against warfarin. In a Phase 2 trial for AF the mean serum creatinine concentration increased by about 10% from baseline in patients treated with AZD0837, which returned to baseline after cessation of therapy. Development of other oral DTIs, such as Sofigatran from Mitsubishi Tanabe Pharma has been discontinued.
  Another strategy for developing oral anticoagulant drugs is that of dual thrombin and fXa inhibitors that some pharmaceutical companies, including Boehringer Ingelheim, have reported on.  These compounds show favorable anticoagulant activity in vitro.